Fungicidal compositions and methods of combating fungi using phthalimidomethyl isothiocyanate

ABSTRACT

Phthalimidomethyl isothiocyanate which possesses fungicidal properties and which may be produced by reacting the corresponding N-chloromethyl-phthalimide, optionally in the presence of a solvent, with a compound which donates the thiocyanate group, e.g., trimethylsilyl isothiocyanate, and alkali metal and ammonium thiocyanates.

United States Patent [191 Zumach et a1.

[451 Apr. 17, 1973 FUNGICIDAL COMPOSITIONS AND METHODS OF COMBATING FUNGI USING PHTHALIMIDOMETHYL ISOTHIOCYANATE Inventors: Gerhard Zumach; Bertram Anders,

both of CologneStammheim; Ferdinand Grewe, Burscheld; Engelbert Kuhle, Berg. Gladbach; Helmut Knapers, Leverkusen, all of Germany Assignee: Farbenfabrikcn Bayer Aktiengesellschaft, Leverkusen, Germany Filed: Oct. 21, 1970 Appl' No.: 82,827

Related US. Application Data Division of Ser. No. 729,547, May 16, 1968, Pat. No. 3,558,650.

Foreign Application Priority Data June 13, 1967 Germany ..F 52666 US. Cl ..424/274 Primary Examiner-Albert T. Meyers Assistant Examinen-Allen .1. Robinson Attorney-Ralph D. Dinklage et a1.

[ 5 ABSTRACT Phthalimidomethyl isothiocyanate which possesses fungicidal properties and which may be produced by reacting the corresponding N-chloromethyl-phthalimide, optionally in the presence of a solvent, with a compound which donates the thiocyanate group, e.g., trimethylsilyl isothiocyanate, and alkali metal and ammonium thiocyanates.

5 Claims, No Drawings filed May 16, 1968, issued as U. S. Pat. No. 3,558,650

on Jan. 26, I971.

The present invention relates to and has for its objects the provision for the particular new isothiocyanate compound phthalimidomethyl isothiocyanate which possesses fungicidal properties, active compositions in the form of mixtures of such compound with solid and liquid dispersible carrier vehicles, and methods for producing such compound and for using such compound in a new way especially for combating fungi, with other and further objects becoming apparent from a study of the within specification and accompanying examples.

It is already known that N-trichloromethylmercapto- 4-cyclohexene-vehicle Z-dicarboximide (A), N-

trichloromethylthiophthalimide (B) as well as zinc ethylene-bis-dithiocarbamate (C) can be used for the control of phytopathogenic fungi (compare German Pat. Nos. 921,290 and 976,686). All these compounds have attained a very great significance in practice.

It has been found in accordance with the present invention that the particular new isothiocyanate compound, i.e. phthalimidomethyl isothiocyanate having the formula 00 I N-CH2NC S exhibits strong fungicidal properties.

It has been furthermore found in accordance with the present invention that a versatile and smooth process for the production of the particular new isothiocyanate of formula (I) above in favorable yields may be provided, which comprises reacting N- chloromethyl-phthalimide having the formula oo (IIa) optionally in the presence of a solvent, with a compound (lb) which donates the thiocyanate group.

Surprisingly, the phthalimidomethyl isothiocyanate of the present invention shows a higher fungicidal activity than the fungicidally active derivatives of phthalimide or tetrahydrophthalimide known from the prior art. The active compound of the invention therefore 5 metal thiocyanates, particularly potassium and sodium thiocyanate, and ammonium thiocyanate.

When trimethysilyl isothiocyanate is used, the reaction is preferably carried out in the absence of a solvent and instead in excess trimethysilyl isothiocyanate. In general, the reaction is carried out at a temperature of about to 200C, preferably at to 170C. The

.reaction can be carried out for example by heating the reaction components together in a distillation apparatus to l50-l60C and, when the splitting off of trimethyl chlorosilane has ended, distilling off the excess trimethysilyl isothiocyanate in a water-jet vacuum. The crystalline residue is the desired product in substantially pure form.

When an alkali metal or ammonium thiocyanate is used, the reaction is desirably carried out in the Y presence of a solvent. As solvent, there may be mentioned for example: hydrocarbons, such as benzene, toluene, etc.; chlorinated hydrocarbons, such as dichloroethane, chloroform, chlorobenzene, etc.; ethers, such as tetrahydrofuran, dionan, etc.; and ketones, such as acetone, methylethyl ketone, etc. Acetone is a preferred solvent. In general, the reaction is carried out at about 50 to C, preferably at the boiling temperature of the solvent. An excess of the thiocyanate reactanct of up to about 100 percent preferably 20-30 percent, has proved advantageous. The reaction time is usually about 5-50 hours, preferably 10-20 hours. The reaction can be carried out for example by adding the alkali metal or ammonium thiocyanate (for example potassium thiocyanate) to a solution of the N-chloromethylphthalimide, and heating the mixture to the boil for 10-20, for example 15, hours with stirring. Filtration while hot is then effected, and the filtrate is evaporated in a vacuum; the crystalline residue is normally recrystallized, for example from benzene/petroleum ether.

Advantageously, the instant active compound exhibits a strong fungitoxic activity. It shows a relatively low toxicity to warm-blooded animals and is therefore suitable for the control of undesired growth of fungi. Its good compatibility with higher plants permits its use as a plant protection agent against fungal plant diseases.

The instant active compound is particularly effective against parasitic fungi on above-the-soil parts of plants, such as Phytophthora species, Fusicladium species, Peronaspora species and Botrytia species. However, it also acts very well against genuine mildew fungi such as Podosphaera species.

The active compound according to the instant invention can be utilized, if desired, in the form of the usual formulations or compositions with diluents or extenders, i.e., dispersible carrier vehicles, such as solutions,

emulsions, suspensions, emulsifiable concentrates, spray powders, pastes, soluble powders, dusting agents, granules, etc. These are prepared in known manner, for instance by extending the active compound with (Ila) (11b) Examples of compounds (IIb) which donate the thiocyanate group are trimethylsilyl isothiocyanate, alkali dispersible liquid diluent carriers and/or dispersible solid carriers optionally with the use of carrier vehicle assistants, e.g., surface-active agents, including emulsifying agents and/or dispersing agents, whereby, for'example, in the case where water is used as diluent, organic solvents may be added as auxiliary solvents (cf. Agricultural Chemicals, March I960, pages 35-38). The following may be chiefly considered for use as carrier vehicles for this purpose: dispersible liquid diluent carriers including organic solvents, such as aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated, especially chlorinated, aromatic hydrocarbons (e.g., chlorobenzenes, etc.), paraffins (e.g., petroleum fractions), chlorinated aliphatic hydrocarbons (e.g., methylene chloride, etc.), alcohols (e.g., methanol, ethanol, propanol, butanol, etc.), amines (e.g., ethanolamine, etc.), ethers, ether-alcohols (e.g., glycol monomethyl ether, etc.), amides (e.g., dimethyl formamide, etc.), sulfoxides (e.g., dimethyl sulfoxide, etc.), ketones (e.g., acetone, etc.), and water; as well as dispersible finely divided solid carriers, such as ground natural minerals (e.g., kaolins, alumina, silica, chalk, i.e., calcium carbonate, talc,

kieselguhr, etc.) and ground synthetic minerals (e.g.,

highly dispersed silicic acid, silicates, e.g., alkali silicates, etc.); whereas the following may be chiefly considered for use as carrier vehicle assistants, e.g., surface-active agents, for this purpose; emulsifying agents, such as non-ionic and anionic emulsifying agents (e.g., polyethylene oxide esters of fatty acids, polyethylene oxide esters of fatty alcohols, alkyl sulfonates, aryl sulfonates, etc., and expecially alkyl aryl-polyglycol ethers, magnesium stearate, sodium oleate, etc.); and dispersing agents, such as lignin, sulfite waste liquors, methyl cellulose, etc.

Such active compound may be employed alone or in the form of mixtures with such solid or liquid dispersible carrier vehicles and/or with other known compatible active agents, especially plant protection agents, such as other fungicides, herbicides, insecticides, bactericides, etc., if desired, or in the form of particular dosage preparations for specific application made therefrom, such as solutions, emulsions, suspensions, powders, pastes, and granules which are thus ready for use.

As concerns commercially marketed preparations, these generally contemplate carriercomposition mixtures in which the active compound is present in an amount substantially between about 0.1-95 percent, and preferably 0.5-90 percent, by weight of the mixture, whereas carrier composition mixtures suitable for direct application or field application generally contemplate those in which the active compound is present in an amount substantially between about 0.00l20 percent, especially 0.0005-5 percent, preferably 0.001-1 percent, by weight of the mixture. Thus, the present invention contemplates overwall compositions which comprise mixtures of a dispersible carrier vehicle such as (l) a dispersible carrier solid, or (2) a dispersible carrier liquid such as an organic solvent and/or water preferably including a carrier vehicle assistant, e.g., surface-active agent, such as an emulsifying agent and/or a dispersing agent, and an amount of the active compound which is effective for the purpose in question and which is generally about 0.0005- percent, and preferably 0.001-95 percent by weight of the mixture.

In particular, the present invention contemplates methods of selectively controlling or combating fungi, which comprises applying to at least one of (a) such fungi and (b) their habitat, a fungicidally effective amount of the particular active compound of the invention alone or together with a carrier vehicle as noted above. The instant formulations or compositions are applied in the usual manner, for instance by spraying, atomizing, vaporizing, scattering, dusting, watering, sprinkling, pouring, and the like.

It will be realized, of course, that the concentration of the particular active compound utilized in admixture with the carrier vehicle will depend upon the intended application. Therefore, in special cases, it is possible to go above or below the aforementioned concentration ranges, e.g., depending on the nature of the application and the species of fungus controlled.

The outstanding fungitoxic effectiveness of the instant compound, as well as the distinct superiority thereof compared with known products of analogous constitution and the same type of activity, can be seen, by way of illustration and without limitation, from the following experimental test results:

EXAMPLE 1 Fusicladium test (apple scab) [Protective] Solvent: 4.7 parts by weight acetone Emulsifier: 0.3 part byweight alkylaryl poly glycol ether Water: 95.0 parts by weight The amount of the particular active compound required for the desired concentration of such active compound in the spray liquid is mixed with the stated amount of solvent, and the resulting concentrate is diluted with the stated amount of water which contains the stated emulsifier to provide the final lower concentration.

Young apple seedlings in the 4-6 leaf stage are sprayed (i.e., treated) with the spray liquid until dripping wet. The plants remain in a greenhouse for 24 hours at 20C and at a relative atmospheric humidity of 70 percent. They are then inoculated with an aqueous conidium suspension of the apple scab causative organism (Fusicladium dendriticum el) and incubated for 18 hours in a humidity chamber at l820C and at a relative atmospheric humidity of percent.

The-plants then again come into a greenhouse for 14 days. 7

15 days after inoculation, the infestation of the seedlings is determined as a percentage of the untreated but also inoculated control plants.

0 percent means no infestation; 100 percent means that the infestation is exactly as great as in thecase of the control plants. I

The particular active compounds tested, their concentrations and the results obtained can be seen from the following Table l.

TABLE 1 Fusicladium test [Protective] Active compound infestation as a percentage of the infestation of the 5 untreated control with a concentration of active compound (in of 0.0062 0.0031 K (A) NSCCla 17 1 (known) I 5 C O NCHz-NCS 3 3 EXAMPLE 2 F usicladium test (apple scab) [Curative] Solvent: 4.7 parts by weight acetone Emulsifier: 0.3 part by weight alkylaryl polyglycol ether Water: 95.0 parts by weight The amount of the particular active compound required for the desired concentration of such active compound in the spray liquid is mixed with the stated amount of solvent, and the resulting concentrate is diluted with the stated amount of water which contains the stated emulsifier to provide the final lower concentration.

Young apple seedlings in the 4-6 leaf stage are inoculated with an aqueous conidium suspension of the apple scab causative organism (Fusicladium dendriticum el) and incubated for 18 hours in a humidity chamber at l8-20C and at an atmospheric humidity of 100 percent. The plants are then placed in a greenhouse where they dry.

After standing for a suitable period of time, the plants are sprayed dripping wet (i.e., treated) with the spray liquid prepared in the manner described above.

' The plants then again are placed in a greenhouse.

15 days after inoculation, the infestation of the apple seedlings is determined as a percentage of the untreated but also inoculated control plants.

0 percent means no infestation; 100 percent means that the infestation is exactly as great as in the case of the control plants.

The particular active compounds tested, their concentrations, the period of time between inoculation and spraying and the results obtained can be seen from the following Table 2.

tion of active compound (in of spraying (B) N-SCCI; 48

(known) (A) N-SCCI; 39

(known) (I) NCHz-NCS 37 EXAMPLE 3 Podosphaera test (powdery mildew of apples) [Protective] Solvent: 4.7 parts by weight acetone Emulsifier: 0.3 part by weight alklaryl polyglycol ether Water: .0 parts by weight The amount of the particular active compound required for the desired concentration of such active compound in the spray liquid is mixed with the stated amount, of solvent, and the resulting concentrate is diluted with the stated amount of water which contains the stated emulsifier to provide the final lower concentration.

Young apple seedlings in the 4-6 leaf stage are sprayed (i.e., treated) with the spray liquid until. dripping wet. The plants remain in a greenhouse for 24 hours at 20C and at a relative atmospheric humidity of 70 percent. They are then inoculated by dusting with conidia of the apple powder mildew causative organism (Podosphaera Ieucotricha Salm.) and placed in a greenhouse at a temperature of 2 l 23C and at a relative atmospheric humidity of about 70 percent.

Ten days after the inoculation, the infestation of the seedlings is determined as a percentage of the untreated but also inoculated control plants.

0 percent means no infestation; percent means that the infestation is exactly as great as in the case of the control plants.

The particular active compounds, their concentrations and the results obtained can be seen from the following Table 3.

TABLE 3 Podosphaera test [Protective] Active compound Infestation as a percentage of the infestation of the untreated control with a concentration of active compound (in of 0. 1

(known) (known) (I) N-CHz NC s 17 55 EXAMPLE 4 l5 Phytophthora test A Solvent: 4.7 parts by weight acetone Dispersing agent: 0.3 part by weight alkylaryl polyglycol ether Water: 95.0 parts by weight The amount of the particular active compound required for the desired concentration of such active compound in the spray liquid is mixed with the stated amount of solvent, and the resulting concentrate is diluted with the stated amount of water which contains the stated dispersing agent to provide the final lower concentration.

Young tomato plants (Bonny best) with 2-6 foliage leaves are sprayed (i.e., treated) with the spray liquid until dripping wet. The plants remain in a greenhouse for 24 hours at 20C and at a relative atmospheric humidity of 70 percent. The tomato plants are then inoculated with an aqueous spore suspension of Phytophthora infestans. The plants are brought into a moist chamber with an atomospheric humidity of 100 percent and a temperature of l8-20C.

After 5 days the infestation of the tomato plants is determined as a percentage of the untreated but likewise inoculated control plants.

0 percent means no infestation; 100 percent means that the infestation is exactly as great as in the case of the control plants.

The particular active compounds tested, their concentrations and the results obtained can be seen from the following Table 4. V

TABLE 4 Active compound 7 compound (in of v 0.025 0.0062 66 (A) N'SCC1; 13 26 (known) co g (B) N-SCCI; 12 26 (known) i CHz-NHC- (C) Zn 1 23 CHz-NH-fi-S s (known) HNCS 2 15 (I) N C co The process for producing the instant compound according to the present invention is illustrated, without limitation, by the following further Examples.

EXAMPLE 5 l06l08C and can be recrystallized from benzene/petroleum ether. M.p. l l4-1 16C.

EXAMPLE6 A mixture of 98g (0.5 mol) of N-chloromethylphthalimide in 300 ml. of acetone and 58g (0.6 mol) of potassium thiocyanate is heated to the boil for 15 hours. After filtration of the warm solution, the solvent is evaporated in a vacuum and the crystalline residue, which still contains a large amount of inorganic salts, is recrystallized from benzene/petroleum ether. 72g (66 percent of the theory) of phthalimidomethyl isothiocyanate are obtained. M.p. ll2.l 15C) It will be realized by the artisan that the instant compound contemplated by the present invention possesses the desired strong fungicidal properties, with regard to a broad spectrum of activity, as well as a comparatively low toxicity toward warm-blooded creatures and a concomitantly low phytotoxicity, enabling such compound to be used with correspondingly favorable compatibility with warm-blooded creatures and plants for more effective control and/or elimination of fungi by application of such compound to such fungi and/or their habitat.

It will be appreciated that the instant specification and examples are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention which is to be limited only by the scope of the appended claims.

What is claimed is:

l. A composition comprising phthalimidomethyl isothiocyanate in admixture with a dispersible carrier vehicle, said isothiocyanate being present in a fungicidally'effective amount and constituting substantially between about 0.0001-95 percent by weight of the composition.

2. The composition according to claim 1 wherein said dispersible carrier vehicle is selected from the group consisting of l) a dispersible finely divided solid and (2) a dispersible carrier liquid selected from the group consisting of an organic solvent, water, and mixtures thereof, said liquid containing a surface-active agent selected from the group consisting of anionic emulsifying agents, non-ionic emulsifying agents, and dispersing agents.

3. A method of combating fungi, which comprises applying to at least one of (a) such fungi and (b) their habitat, a fungicidally effective amount of a composition according to claim 1.

4. The method according to claim 3, wherein such phthalimidomethyl isothiocyanate is used in the form of a mixture with a dispersible carrier vehicle, said 

2. The composition according to claim 1 wherein said dispersible carrier vehicle is selected from the group consisting of (1) a dispersible finely divided solid and (2) a dispersible carrier liquid selected from the group consisting of an organic solvent, water, and mixtures thereof, said liquid containing a surface-active agent selected from the group consisting of anionic emulsifying agents, non-ionic emulsifying agents, and dispersing agents.
 3. A method of combating fungi, which comprises applying to at least one of (a) such fungi and (b) their habitat, a fungicidally effective amount of a composition according to claim
 1. 4. The method according to claim 3, wherein such phthalimidomethyl isothiocyanate is used in the form of a mixture with a dispersible carrier vehicle, said isothiocyanate being present in a fungicidally effective amount and constituting substantially between about 0.0001-20 percent by weight of the mixture.
 5. The method according to claim 4 wherein said dispersible carrier vehicle is selected from the group consisting of (1) a dispersible finely divided solid and (2) a dispersible carrier liquid selected from the group consisting of an organic solvent, water, and mixtures thereof, said liquid containing a surface-active agent selected from the group consisting of anionic emulsifying agents, non-ionic emulsifying agents, and dispersing agents. 